CN109985279A - It is a kind of to be compounded with the micro-patterning nano-fiber material and its preparation method and application for carrying medicine MOF - Google Patents

It is a kind of to be compounded with the micro-patterning nano-fiber material and its preparation method and application for carrying medicine MOF Download PDF

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CN109985279A
CN109985279A CN201910263578.9A CN201910263578A CN109985279A CN 109985279 A CN109985279 A CN 109985279A CN 201910263578 A CN201910263578 A CN 201910263578A CN 109985279 A CN109985279 A CN 109985279A
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micro
patterning
nano
zif
nano particle
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CN109985279B (en
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徐合
柯勤飞
李锦绣
吕方
张天帅
徐雅凤
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Shanghai Normal University
University of Shanghai for Science and Technology
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Shanghai Normal University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222—Gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/60—Materials for use in artificial skin
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F1/00—General methods for the manufacture of artificial filaments or the like
    • D01F1/02—Addition of substances to the spinning solution or to the melt
    • D01F1/10—Other agents for modifying properties
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
    • D01F8/02—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from cellulose, cellulose derivatives, or proteins
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
    • D01F8/04—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers
    • D01F8/14—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers with at least one polyester as constituent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/21—Acids
    • A61L2300/214—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures
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    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602—Type of release, e.g. controlled, sustained, slow
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces

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Abstract

The invention belongs to technical field of biological material, are related to a kind of micro-patterning nano-fiber material and its preparation method and application for being compounded with and carrying medicine MOF.The material is using the hydrophily composite electrostatic spinning nanofiber being intertwined as skeleton, ordered arrangement micro-patterning structure, and is distributed the porous structure of open three-dimensional perforation；Hydrophily composite electrostatic spinning nanofiber is the blend of the metal organic frame nano particle of supportive biocompatible material, hydrophily biocompatible material and load repairing activity molecule.Preparation method are as follows: spinning solution, electrostatic spinning preparation are made with the organic solvent of the evenly dispersed metal organic frame nano particle for having load repairing activity molecule, supportive bioactive materials and hydrophihc bioactive material.The material is based on sustained and controlled release medicament Carriers Active and biological tissue activity, and collaboration promotes activity of the cell in body environment and micro-patterning nano-fiber material, is conducive to tissue repair and wound healing, is used to prepare wound repair material.

Description

It is a kind of to be compounded with the micro-patterning nano-fiber material and preparation method thereof for carrying medicine MOF And application
Technical field
The invention belongs to technical field of biological material, and in particular to a kind of to be compounded with the micro-patterning nanofiber material for carrying medicine MOF Material and its preparation method and application.
Background technique
Foot ulcers are one of diabetes major complications, surface of a wound protracted course of disease, and serious person need to even cut toe/limb treatment, Postoperative five year mortality rate is up to 50%~68%.The generally timely and orderly self-regeneration of energy of normal skin wound, and glycosuria Then angiogenesis is insufficient, wound healing is slow for sick wound, and this is mainly due to the growth factors of Angiogensis under high saccharide ring border Secretion is reduced, and corresponding expression of receptor is reduced, and apposition is reduced, microenvironment needed for can not forming wound healing.
In recent years the skin tissue engineering risen utilizes artificial synthesized dermal scaffold material, in conjunction with growth factor, drug Or inorganic particle etc. constructs tissue engineering skin, effectively treatment and reparation skin injury.
Electrospun nano-fibers material has the advantage in more structure, the nanofiber prepared by electrostatic spinning technique The material overwhelming majority is film-form, is preferably attached at the surface of a wound, and quality is frivolous to be caused to bear to the surface of a wound, and is also had same The similar nanofibrous structures of native human's extracellular matrix (ECM) and biggish specific surface area, can promote skin histology The adherency and growth of cell on it, the biography of nutriment needed for good hole connectivity is also beneficial to surface of a wound region cell Defeated and gas exchange, the in recent years extensive attention as skin tissue engineering scaffold by researcher.
Native human's extracellular matrix (ECM) depends not only on the company of rising in extracellular matrix to the regulation of all physiological activities The supporting structure for the effects of connecing, support and protecting additionally depends on the micro- of the support cell life phenomenon stored in extracellular matrix Environment.
Though the effects of playing connection, support and protection in Electrospun nano-fibers material analog natural extracellular matrix Supporting structure, but the microenvironment of support cell life phenomenon (be especially proliferated, migrate, differentiating phenomenon), Wu Faman can not be provided Demand of the sufficient body to the special physiologicals function such as wound repair, especially when human body itself microenvironment is by destroying, to being applied to The requirement of the Electrospun nano-fibers material of the special physiologicals function such as wound repair is higher.
Small molecule substitute of the dimethyl oxalyl glycine (DMOG) as growth factor can induce hypoxia inducible factor 1α(HIF-1α).However transition is using DMOG that there are side effects, such as a large amount of angiogenesis is promoted to lead oncogenic formation and increasing Add RBC acceptor garland rate etc..If can control DMOG slow release in vivo, make its control within the scope of safe concentration, realizes that treatment is made With while, reduce or exempt toxic side effect, will be enlarged by DMOG be applied to tissue repair medical applications.
With flourishing for nanotechnology, metal organic frame (MOFs) be develop in the past 20 years it is extremely rapid novel Organic-inorganic nano porous material, it is to pass through coordination with organic ligand molecule centered on metal ion or metal cluster unit Act on the porous crystalline material that the one kind being self-assembly of has periodic three-dimensional net structure.MOFs have high-sequential, The advantages that huge specific surface area and porosity, is widely used in gas separation, catalysis, sensing and drug loading etc..
Zeolitic imidazolate framework material (ZIF) is one kind of MOFs, has topological structure similar with zeolite molecular sieve, heat Stability and water stability are higher, and specific surface area reaches 1900m2·g-1, aperture isPharmaceutical carrier is acted not only as, together When also have both the effect of diagnosticum, be widely used in biomedicine field.Such as containing the ZIF-67 of cobalt ions, it was widely used as The precursor of metal oxide is crossed, energy storage, biosensor, supercapacitor etc. are applied to.
The present invention is based on the pharmaceutical carrier of metal organic frame porous crystalline state activity and electrostatic spinning techniques, prepare compound gold Belong to the Electrospun nano-fibers material of organic frame particle, which not only has similar to ECM Supporting structure the effects of playing connection, support and protection, compound metal organic frame in Electrospun nano-fibers material The also sustainable slow-release controlled-release wound repair bioactive molecule of particle, forms promoting growth of cell in Electrospun nano-fibers material The microenvironment of (proliferation, migration and differentiation etc.), provides growing tissue for wound repair；Meanwhile Electrospun nano-fibers material As the carrier of repairing activity molecule, in repairing activity molecule it is also sustainable be discharged into body environment, stimulate body ring Border cell activity repairs body environment.
Summary of the invention
The present invention is intended to provide a kind of be compounded with the micro-patterning nano-fiber material for carrying medicine MOF, the micro-patterning nanometer Fibrous material is as pharmaceutical carrier, with Continuous slow release, controlled release activity, the interior repairing activity molecule elder generation Continuous slow release loaded of MOF, In controlled release to micro-patterning nano-fiber material, formed have supporting structure similar with ECM and microenvironment, supporting structure with it is micro- Environment synergistic effect provides bioactivity tissue for cell growth；Repairing activity molecule in micro-patterning nano-fiber material Slow-release controlled-release stimulates and improves body environment cell activity into body environment again, repairs body environment；The micro-patterning is received Rice fibrous material collaboration promotes activity of the cell in body environment and micro-patterning nano-fiber material, be conducive to tissue repair and Wound is efficient, safety heals.
The present invention also provides the preparation method of the above-mentioned micro-patterning nano-fiber material for being compounded with load medicine MOF, the preparations Method is simple to operation, environmental-friendly, low in cost.
The present invention also provides the applications of the above-mentioned micro-patterning nano-fiber material for being compounded with load medicine MOF.
The technical scheme is that a kind of be compounded with the micro-patterning nano-fiber material for carrying medicine MOF, with interlaced The hydrophily composite electrostatic spinning nanofiber of arrangement is skeleton, ordered arrangement micro-patterning structure, and be distributed open three-dimensional The porous structure of perforation；Hydrophily composite electrostatic spinning nanofiber is supportive biocompatible material, hydrophily bio-compatible The blend of the metal organic frame nano particle of material and load repairing activity molecule.
The supportive biocompatible material includes l-lactic acid, polycaprolactone, chitosan or chitin etc., preferably L-lactic acid.
The hydrophily biocompatible material includes gelatin or hyaluronic acid etc., preferably gelatin.
The metal organic frame nano particle is preferably centered on cobalt ions, with organic ligand molecule Coordinate self-assembly The porous crystalline of the three-dimensional net structure of formation, the zeolite imidazole skeleton crystal more preferably formed centered on cobalt ions；Make It is ZIF-67 crystal for preferred embodiment.
The partial size of the metal organic frame nano particle is 50~500nm, preferably 100~200nm；Load, which is repaired, lives Property molecule before, the specific surface area of metal organic frame nano particle is 1500~2000m2/ g, aperture are less than 5nm, preferably less In 2nm, more preferably 1~2nm, pore volume is 0.5~3cm3/g。
The repairing activity molecule includes repairing activity drug and/or the natural repairing activity factor, natural repairing activity because Son is growth factor, and repairing activity drug is preferably small molecule repairing activity drug, such as DMOG.
Micro-patterning structure by be spaced apart from each other be in laterally, longitudinally, laterally with longitudinally perpendicular or laterally and longitudinally multi-angle phase Mutually cross arrangement, size adjustable multiple unit cell pattern compositions, unit cell pattern includes circle, ellipse, parallelogram, ladder Shape or regular polygon (n≤5), parallelogram is preferably rectangle, diamond shape, rectangular；Unit cell pattern is preferably circular or oval, More preferably 30~500 μm of circles of radius；It preferably, is 300~500 μm of circles of radius.
10~1000nm of diameter of hydrophily composite electrostatic spinning nanofiber, preferably 80~450nm, more preferably 150~300nm is preferably 200nm.
In hydrophily composite electrostatic spinning nanofiber, supportive bioactive materials, hydrophihc bioactive material with The mass ratio for loading the metal organic frame nano particle of repairing activity molecule is 1:0.5~2:0.5 × 10-3~5 × 10-3, excellent It is selected as 1:0.9~1.2:1 × 10-3~3 × 10-3, more preferably 1:0.9~1.2:1.5 × 10-3~2 × 10-3。
Hydrophily composite electrostatic spinning nanofiber low-density at micro-patterning structure deposits, between micro-patterning structure High density deposition, Electrospun nano-fibers are based on this regular deposition, form micro- figure of the density interphase of ordered arrangement Patterned nanometer fibrous material improves porosity, the more conducively migration of cell and the transmission of nutriment.
As a preferred solution of the present invention, a kind of to be compounded with the micro-patterning nano-fiber material for carrying medicine MOF, mutually to hand over The hydrophily composite electrostatic spinning nanofiber of mistake arrangement is skeleton, ordered arrangement micro-patterning structure, and be distributed open three Tie up the porous structure of perforation；Hydrophily composite electrostatic spinning nanofiber is l-lactic acid, gelatin and load dimethyl oxalyl The blend of the ZIF-67 nano particle of glycine.
The partial size of ZIF-67 nano particle is 50~500nm, preferably 100~200nm；Load dimethyl oxalyl glycine Before, the specific surface area of ZIF-67 nano particle is 1500~2000m2/ g, aperture are less than 5nm, preferably no greater than 2nm, more preferably For 1~2nm, pore volume is 0.5~3cm3/g；After loading dimethyl oxalyl glycine, the specific surface area of ZIF-67 is 1000~ 1400m2/ g, aperture are less than 5nm, preferably no greater than 2nm, more preferably 1~2nm, and pore volume is 0.5~3cm3/g；With ZIF-67 The quality meter of nano particle, the drugloading rate of dimethyl oxalyl glycine are 200~360mg/g, preferably 300~360mg/g.
Micro-patterning structure by be spaced apart from each other be in laterally, longitudinally, laterally with longitudinally perpendicular or laterally and longitudinally multi-angle phase Mutually cross arrangement, size adjustable multiple unit cell pattern compositions, unit cell pattern includes circle, ellipse, parallelogram, ladder Shape or regular polygon (n≤5), parallelogram is preferably rectangle, diamond shape, rectangular；Unit cell pattern is preferably circular or oval, More preferably 30~500 μm of circles of radius；It preferably, is 300~500 μm of circles of radius.
10~1000nm of diameter of hydrophily composite electrostatic spinning nanofiber, preferably 80~450nm, more preferably 150~300nm is preferably 200nm.
In hydrophily composite electrostatic spinning nanofiber, l-lactic acid, gelatin and load dimethyl oxalyl glycine The mass ratio of ZIF-67 nano particle is 1:0.5~2:0.5 × 10-3~5 × 10-3, preferably 1:0.9~1.2:1 × 10-3~3 ×10-3, more preferably 1:0.9~1.2:1.5 × 10-3~2 × 10-3。
Above-mentioned to be compounded with the preparation method for carrying the micro-patterning nano-fiber material of medicine MOF, step includes: using micro- pattern The reception template of change, it is living with the evenly dispersed metal organic frame nano particle for having load repairing activity molecule, supportive biology Property material and the organic solvent of hydrophihc bioactive material make spinning solution, electrostatic spinning preparation is compounded with the micro- figure for carrying medicine MOF Patterned nanometer fibrous material.
In spinning solution, the gold of supportive bioactive materials, hydrophihc bioactive material and load repairing activity molecule The mass ratio for belonging to organic frame nano particle is 1:0.5~2:0.5 × 10-3~5 × 10-3, preferably 1:0.9~1.2:1 × 10-3~3 × 10-3, more preferably 1:0.9~1.2:1.5 × 10-3~2 × 10-3；Supportive bioactive materials and hydrophily biology The ratio of the volume of the gross mass and organic solvent of active material is 1g:5~20mL, preferably 1g:20mL.
The supportive biocompatible material includes l-lactic acid, polycaprolactone, chitosan or chitin etc., preferably L-lactic acid.
The hydrophily biocompatible material includes gelatin or hyaluronic acid etc., preferably gelatin.
The metal organic frame nano particle is preferably centered on cobalt ions, with organic ligand molecule Coordinate self-assembly The porous crystalline of the three-dimensional net structure of formation, the zeolite imidazole skeleton crystal more preferably formed centered on cobalt ions；Make It is ZIF-67 nano particle for preferred embodiment.
The repairing activity molecule includes repairing activity drug and/or the natural repairing activity factor, natural repairing activity because Son is growth factor, and repairing activity drug is preferably small molecule repairing activity drug, such as DMOG.
Organic solvent includes hexafluoroisopropanol, methylene chloride, chloroform or trifluoroethanol etc., preferably hexafluoroisopropanol (HFIP)。
The parameter of electrostatic spinning are as follows: room temperature, 40%RH~60%RH, application voltage are 7~9kV, and solution fltting speed is It is 8~12cm that 0.01~0.03mL/min, spray head and patterning, which receive the distance between template,.
Electrostatic spinning preparation is compounded with micro-patterning nano fibrous membrane vacuum drying treatment 8~48 hours of load medicine MOF, with Remove residual solvent.
The preparation step for loading the metal organic frame nano particle of repairing activity molecule includes: metal organic frame nanometer Particle is dipped in the solution containing repairing activity molecule, and repairing activity molecule is carried on the duct of metal organic frame nano particle It is interior, form the metal organic frame nano particle of load repairing activity molecule.
In solution containing repairing activity molecule, the concentration of repairing activity molecule is 2~50mg/ml, preferably 15~ 25mg/ml, more preferably 25mg/ml.Phosphate solution preferably containing repairing activity molecule, pH=7.3~7.5 are more excellent It is selected as pH=7.4.
It is impregnated 12~200 hours in 25 DEG C~37 DEG C, temperature is preferably 37 DEG C, and the preferably time is 24~168 hours.
The metal organic frame nano particle is preferably centered on cobalt ions, with organic ligand molecule Coordinate self-assembly The porous crystalline of the three-dimensional net structure of formation, the zeolite imidazole skeleton crystal more preferably formed centered on cobalt ions；Make It is ZIF-67 nano particle for preferred embodiment.
The partial size of metal organic frame nano particle is 50~500nm, preferably 100~200nm；Load repairing activity point Before son, the specific surface area of metal organic frame nano particle is 1500~2000m2/ g, aperture are less than 5nm, preferably no greater than 2nm, more preferably 1~2nm, pore volume are 0.5~3cm3/g。
The repairing activity molecule includes repairing activity drug and/or the natural repairing activity factor, natural repairing activity because Son is growth factor, and repairing activity drug is preferably small molecule repairing activity drug, such as DMOG.
The preparation step of metal organic frame nano particle includes: that metal salt and organic ligand molecule are dissolved in organic solvent In, reaction prepares metal organic frame nano particle under constant temperature and stirring condition.
In organic solvent, the concentration of metallic element is 20~80mmol/L, preferably 65~70mol/L；Metallic element with The molar ratio of organic ligand molecule is 1:5~10, preferably 1:5~8；Organic solvent includes methanol, ethyl alcohol or N-N dimethyl methyl Amide, preferably methanol.
Reaction temperature be 20 DEG C~30 DEG C, preferably room temperature.
After reaction, it is centrifuged, washing, and is dried in vacuo, obtain metal organic frame nano particle.Metal organic frame The partial size of nano particle is 50~500nm, preferably 100~200nm；Specific surface area is 1500~2000m2/g；Aperture is less than 5nm, preferably no greater than 2nm, more preferably 1~2nm；Pore volume is 0.5~3cm3/g。
The metal salt is preferably cobalt salt, such as cobalt chloride or cobalt nitrate.
The organic ligand molecule is preferably 2-methylimidazole.
As a preferred solution of the present invention, a kind of to be compounded with the preparation side for carrying the micro-patterning nano-fiber material of medicine MOF Method, step include: the reception template using micro-patterning, are received with the evenly dispersed ZIF-67 for having load dimethyl oxalyl glycine The organic solvent of rice grain, l-lactic acid and gelatin makees spinning solution, and electrostatic spinning preparation is compounded with the micro-patterning for carrying medicine MOF Nano fibrous membrane.
In spinning solution, the quality of the ZIF-67 nano particle of l-lactic acid, gelatin and load dimethyl oxalyl glycine Than for 1:0.5~2:0.5 × 10-3~5 × 10-3, preferably 1:0.9~1.2:1 × 10-3~3 × 10-3, more preferably 1:0.9 ~1.2:1.5 × 10-3~2 × 10-3；The ratio of the volume of the gross mass and organic solvent of l-lactic acid and gelatin is 1g:5 ~20mL, preferably 1g:20mL.The molecular weight of l-lactic acid is 100,000~1,000,000, preferably 200,000~500,000.
Organic solvent includes hexafluoroisopropanol, methylene chloride, chloroform or trifluoroethanol etc., preferably hexafluoroisopropanol (HFIP)。
The parameter of electrostatic spinning are as follows: room temperature, 40%RH~60%RH, application voltage are 7~9kV, and solution fltting speed is It is 8~12cm that 0.01~0.03mL/min, spray head and patterning, which receive the distance between template,.
The preparation step for loading the ZIF-67 nano particle of dimethyl oxalyl glycine includes: that ZIF-67 nano particle is dipped in In solution containing DMOG, dimethyl oxalyl glycine is carried in the duct of ZIF-67 nano particle, forms load dimethyl The ZIF-67 nano particle of oxalyl glycine.
In solution containing DMOG, the concentration of DMOG is 2~50mg/ml, preferably 15~25mg/ml, more preferably 25mg/ml.Preferably containing the phosphate solution of DMOG, pH=7.3~7.5, more preferably pH=7.4.
It is impregnated 12~200 hours in 25 DEG C~37 DEG C, temperature is preferably 37 DEG C, and the preferably time is 24~168 hours.
The partial size of ZIF-67 nano particle is 50~500nm, preferably 100~200nm；Load dimethyl oxalyl glycine Before, the specific surface area of ZIF-67 nano particle is 1500~2000m2/ g, aperture are 1~2nm, and pore volume is 0.5~3cm3/g； After loading dimethyl oxalyl glycine, the specific surface area of ZIF-67 is 1000~1400m2/ g, aperture are 1~2nm, and pore volume is 0.5~3cm3/g；In terms of the quality of ZIF-67 nano particle, the drugloading rate of dimethyl oxalyl glycine is 200~360mg/g, Preferably 300~360mg/g.
The preparation step of ZIF-67 nano particle includes: that cobalt salt and 2-methylimidazole are dissolved in organic solvent, and constant temperature is simultaneously Reaction preparation ZIF-67 nano particle under stirring condition.
In organic solvent, the concentration of cobalt element is 20~80mmol/L, preferably 65~70mmol/L；Cobalt element and 2- first The molar ratio of base imidazoles is 1:5~10, preferably 1:5~8；Organic solvent includes methanol, ethyl alcohol, N-N dimethylformamide, excellent It is selected as methanol.
Reaction temperature be 20 DEG C~30 DEG C, preferably room temperature.
After reaction, it is centrifuged, washing, and is dried in vacuo, obtain ZIF-67 nano particle.The grain of ZIF-67 nano particle Diameter is 50~500nm, preferably 100~200nm；Specific surface area is 1500~2000m2/g；Aperture is micropore, preferably 1~ 2nm；Pore volume is 0.5~3cm3/g。
It is prepared by the present invention to be compounded with the micro-patterning nano-fiber material for carrying medicine MOF, with l-lactic acid, gelatin and bear It is skeleton that the hydrophily composite electrostatic spinning nanofiber to be formed, which is blended, in the ZIF-67 nano particle for carrying dimethyl oxalyl glycine, The porous structure of the open three-dimensional perforation of distribution, and it is aided with the micro-patterning structure of ordered arrangement.It is born in ZIF-67 nano particle The dimethylglycine of load first out of ZIF-67 nano particle Continuous slow release, in controlled release to micro-patterning nano-fiber material, then Continuous slow release, controlled release reach sustained release and controlled-release effect into body environment out of micro-patterning nano-fiber material, meanwhile, cobalt Ion can be from Continuous slow release of degrading in ZIF-67 nano particle, in controlled release to micro- pattern nano-fiber material, and from micro-patterning Continuous slow release, controlled release are into body environment in nano material, in the process, are formed and are conducive in micro-patterning nano-fiber material Cell growth (proliferation, adherency, migration, at vascularization, collagen deposition and inhibit inflammatory reaction) by dimethylglycine and cobalt The microenvironment of ion synergistic effect, cooperates with the supporting structure of micro- pattern nano-fiber material, forms the tissue for being conducive to cell growth； And the microenvironment that the dimethylglycine formed in micro-patterning nano-fiber material acts synergistically with cobalt ions also releasably arrives In body environment, stimulates and promote the proliferation of body environment cell, adherency, migration, at vascularization, collagen deposition and inhibits inflammation Body environment is repaired in reaction.
What formation was stable in micro-patterning nano-fiber material prepared by the present invention is conducive to cell is grown and native human The similar supporting structure of extracellular matrix and microenvironment provide bioactivity tissue for body cell；Meanwhile the micro-patterning is received The microenvironment formed in it slow, controlled release can also be put into body environment as carrier, stimulate and promote body by rice fibrous material Body environment is repaired in the growth of ambient cell；The micro-patterning nano-fiber material cooperates with sustained and controlled release medicament Carriers Active and life Object tissue activity, collaboration promote growth activity of the cell in body environment and micro-patterning nano-fiber material, promote body Wound repair.
To sum up, it is compounded with the micro-patterning nano-fiber material for carrying medicine MOF, it can be in micro-patterning nano-fiber material The supporting structure and microenvironment similar with native human's extracellular matrix are formed, the bioactivity group for being conducive to cell growth is formed It knits, which can also be aided with active metallic ion by the repairing activity molecular composition loaded in MOF when necessary；And it can will be micro- The microenvironment slow release formed in patterned nano-fiber material is into body environment；It is compounded with the micro-patterning for carrying medicine MOF The sustained and controlled release medicament Carriers Active and biological tissue activity of nano-fiber material, collaboration promote cell in body environment and micro- pattern Change the growth activity in nano-fiber material, promotes wound repair.
Therefore, the micro-patterning nano-fiber material that the present invention is compounded with load medicine MOF can be used for preparing wound repair material, It is particularly suitable for efficient, the safety healing of diabetic wounds.
A kind of biomaterial has wound repair activity, the micro-patterning Nanowire for carrying medicine MOF is compounded with containing the present invention Tie up material.
Compared with the existing technology, the present invention has the advantages that the present invention is compounded with the micro-patterning nanofiber for carrying medicine MOF Material is acted on based on the slow-release controlled-release of its own, can be formed in micro-patterning nano-fiber material and is conducive to the micro- of cell growth Environment cooperates with the supporting structure of micro-patterning nano-fiber material, forms the bioactivity tissue for being conducive to cell growth；Micro- pattern Change the also sustainable slow-release controlled-release of microenvironment for being conducive to cell growth formed in nano-fiber material into body environment, stimulation Body cell growth, repairs body environment；The micro-patterning nano-fiber material for carrying medicine MOF is compounded with based on sustained and controlled release medicament load Body activity and biological tissue activity, collaboration promote growth of the cell in body environment and micro-patterning nano-fiber material living Property, it is conducive to tissue repair and wound healing.
Detailed description of the invention
SEM (A), TEM (B), EDS (C), XRD (D), the nitrogen adsorption desorption for the ZIF-67 that Fig. 1 is prepared for embodiment 1 are bent Line chart (E, F) and graph of pore diameter distribution (G).
Fig. 2 is PLLA/Gel micro-patterning nano fibrous membrane (PL/G, A prepared by embodiment 11、A2、A3)、ZIF-67/ PLLA/Gel micro-patterning nano fibrous membrane (Z-PL/G, B1、B2、B3) and DMOG@ZIF-67/PLLA/Gel micro-patterning nanometer Tunica fibrosa (DZ-PL/G, C1、C2、C3) optical microscopy map, scanning electron microscope (SEM) photograph and transmission electron microscope picture.
Fig. 3 is the external DMOG release of DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane prepared by embodiment 1 Curve graph (A) and Co plasma diffusing W,Mo curve graph (B).
Fig. 4 is PLLA/Gel micro-patterning nano fibrous membrane (PL/G), ZIF-67/PLLA/Gel micro-patterning nanofiber Under film (Z-PL/G) and DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) effect, HUVECs (A), The proliferation histogram of HaCaT (B), HAF (C).
Fig. 5 is PLLA/Gel micro-patterning nano fibrous membrane (PL/G), ZIF-67/PLLA/Gel micro-patterning nanofiber Under film (Z-PL/G) and DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) effect, HUVECs cell Transwell transition graph (A, B, C) and quantitative analysis (D).
Fig. 6 is PLLA/Gel micro-patterning nano fibrous membrane (PL/G), ZIF-67/PLLA/Gel micro-patterning nanofiber Under film (Z-PL/G) and DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) effect, HUVECs cell At vessel graph (A, B, C) and quantitative analysis (D).
Fig. 7 is PLLA/Gel micro-patterning nano fibrous membrane (PL/G), ZIF-67/PLLA/Gel micro-patterning nanofiber Under film (Z-PL/G) and DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) effect, HUVECs is at blood The expression quantity of pipe related gene VEGF (A), eNOS (B), HIF-1 α (C).
Fig. 8 is the 0th, 3,7,9 and 11 day after operation, and control group, PL/G group, Z-PL/G group and DZ-PL/G group diabetes are small Mouse midline incision healing figure (A), notch reparation simulation effect picture (B) and notch repair statistical chart (C).
Fig. 9 is control group, PL/G group, Z-PL/G group and DZ-PL/G group diabetic mice back the 7th and 11 day after operation Incision new vessels figure (A) and new vessels quantitative analysis figure (B, C).
Figure 10 is control group, PL/G group, Z-PL/G group and DZ-PL/G group diabetic mice notch the 7th and 11 day after operation The dyeing of CD31 early stage blood vessel, DAPI nuclear targeting and the Merge vascularization colored graph (A, B) at place；And the 7th and 11 after operation It, angiogenesis quantitative analysis (C, D).
Figure 11 is control group, PL/G group, Z-PL/G group and DZ-PL/G group diabetic mice notch the 7th and 11 day after operation Histotomy Massion trichrome stain figure (A, B) and collagen expression quantitative analysis (C, D).
Figure 12 is control group, PL/G group, Z-PL/G group and DZ-PL/G group diabetic mice incision type i collagen (A), III The Q-PCR expression result chart of Collagen Type VI (B), Ki67 (C) and TGF-β (D).
Figure 13 is control group, PL/G group, Z-PL/G group and DZ-PL/G group diabetic mice incision proinflammatory cytokine IL-10 (A), IL-6 (B), IL-1 β (C) gene expression results figure.
Specific embodiment
The present invention will be further explained below with reference to examples, but they are not to impose any restrictions to the present invention.
The preparation of 1 micro-patterning nano fibrous membrane of embodiment
(1) ZIF-67 of ZIF-67 (zeolite imidazole class framework material) and loading DMOG (dimethyl oxalyl glycine) Preparation and its Morphological Characterization
1. preparing ZIF-67 nano particle
0.291g cobalt nitrate hexahydrate and 0.66g 2-methylimidazole are dissolved in 15mL methanol respectively, are mixed at room temperature For 24 hours, 5min products therefrom is centrifuged under 10000rpm, after being washed repeatedly with methanol, in 80 DEG C of vacuum drying for 24 hours to get ZIF- 67 nano particles, SEM, TEM, EDS, XRD, nitrogen adsorption desorption curve are as shown in Figure 1.
2. preparation carries medicine ZIF-67 nano particle
At 37 DEG C, 25mg ZIF-67 is placed in DMOG phosphate buffer solution (PBS, the pH=that concentration is 15mg/mL 7.4) it is impregnated 3 days in, after being centrifuged and washing, ZIF-67 (the DMOG@ZIF- for obtaining loading DMOG for 24 hours is dried in vacuo at 37 DEG C 67) nano particle, XRD, nitrogen adsorption desorption curve are as shown in Figure 1.
By SEM figure (Figure 1A) and the TEM figure (Figure 1B) of ZIF-67 nano particle it is found that the crystal class of ZIF-67 nano particle Type is consistent, and uniform in size, and particle size range is 50~500nm, and partial size is distributed in 100~200nm more.ZIF-67 nanometers of DMOG@ The SEM figure and TEM figure of particle are the same as Figure 1A and Figure 1B.
By the EDS figure (Fig. 1 C) of ZIF-67 nano particle it is found that containing cobalt element in ZIF-67 nano particle.
By the XRD diagram (Fig. 1 D) of ZIF-67 nano particle and DMOG@ZIF-67 nano particle it is found that ZIF-67 nano particle Peak position, peak shape and the relative intensity of XRD diagram, the theoretical XRD spectra with software simulation matches, it is confirmed that the present embodiment system The ZIF-67 nano particle of standby pure phase.Compared with the XRD diagram of F-67 nano particle, the peak intensity of DMOG@ZIF-67 nano particle It dies down, peak position and peak shape are to change.
By nitrogen adsorption-desorption curve of ZIF-67 nano particle (Fig. 1 E) and DMOG@ZIF-67 nano particle (Fig. 1 F) It is found that nitrogen adsorption-desorption curve of ZIF-67 nano particle and DMOG@ZIF-67 nano particle belongs to I type adsorption isotherm, In lower relative barometric pressure, nitrogen adsorption is sharply increased, and illustrates to be distributed micropore in ZIF-67 nano particle, as Fig. 1 G is shown； Relative pressure continues growing, and nitrogen increases trend and slows down, in relative pressure P/P0Small hysteresis loop, explanation are shown when > 0.9 Occasionally have mesoporous in ZIF-67 nano particle, mesoporous number is more micro.
By the nitrogen adsorption desorption of table 1, analysis shows, compared to ZIF-67, the specific surface area of DMOG@ZIF-67 has obvious drop Low, aperture and pore volume edge down low a bit, and the drugloading rate of ZIF-67 is that (1g ZIF-67 can load 359.12mg to 359.12mg/g DMOG), efficiency of loading 23.9%.
Table 1.ZIF-67 and the structural parameters of DMOG@ZIF-67 and the efficiency of loading of ZIF-67
(2) preparation and its form and the hydrophilic and hydrophobic of the micro-patterning nano fibrous membrane of ZIF-67 nano particle are compounded with The characterization of energy
Respectively by ZIF-67 and DMOG@ZIF-67 ultrasonic disperse in hexafluoroisopropanol (HFIP), correspondence obtains concentration and is The ZIF-67 suspension and DMOG@ZIF-67 suspension of 0.004g/100mL.
The l-lactic acid for being 1:1 by mass ratio is separately added into ZIF-67 suspension and DMOG@ZIF-67 suspension The gross mass of (molecular weight 300,000, PLLA) and gelatin (Gel), l-lactic acid and gelatin and the ratio of HFIP volume are 5g: 100mL is respectively formed the spinning solution containing ZIF-67 and the spinning solution containing DMOG@ZIF-67.
It is simultaneously 1:1, l-lactic acid according to l-lactic acid (molecular weight 300,000, PLLA) and gelatin (Gel) mass ratio It is 5g:100mL with the gross mass of gelatin and the ratio of HFIP volume, preparation not only without containing ZIF-67 but also did not contained DMOG ZIF- 67 parallel control spinning solution.
Parallel control spinning solution, the spinning solution containing ZIF-67 and the spinning solution containing DMOG@ZIF-67, using patterning Template is received, under the conditions of room temperature, 50%RH, electrostatic spinning prepares corresponding patterned porous composite electrospun tunica fibrosa And (24 hours) are dried in vacuo, it is followed successively by PLLA/Gel micro-patterning nano fibrous membrane (PL/G), the micro- figure of ZIF-67/PLLA/Gel Patterned nanometer tunica fibrosa (Z-PL/G) and DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G).
The parameter of electrostatic spinning are as follows: application voltage is 7kV, and solution fltting speed is 0.02mL/min, spray head and patterning Receiving the distance between template is 10cm.
Using optical microscopy, scanning electron microscope (SEM), transmission electron microscope (TEM) and contact angle (WCA) to the micro- of above-mentioned preparation The object phase composition of patterned nano-fiber film and surface microstructure are analyzed and are characterized.It is measured by Image J software fine Diameter and aperture are tieed up, 100 fibers are at least measured from SEM image and calculate its avarage fiber diameter.
The optical microscopy map of PLLA/Gel micro-patterning nano fibrous membrane (PL/G) such as Fig. 2 (A1), scanning electron microscope (SEM) photograph such as Fig. 2 (A2), transmission electron microscope picture such as Fig. 2 (A3)；The optical microscopy map of ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (Z-PL/G) Such as Fig. 2 (B1), scanning electron microscope (SEM) photograph such as figure (B2), transmission electron microscope picture such as Fig. 2 (B3)；DMOG@ZIF-67/PLLA/Gel micro-patterning The optical microscopy map of nano fibrous membrane (DZ-PL/G) such as Fig. 2 (C1), scanning electron microscope (SEM) photograph such as Fig. 2 (C2), transmission electron microscope picture such as Fig. 2 (C3)。
PLLA/Gel micro-patterning nano fibrous membrane (PL/G), ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (Z- PL/G) and the water contact angle of DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) be followed successively by 28 °, 29 °, 30 °, by Fig. 2A1-C1It is found that being all had on PL/G, Z-PL/G and DZ-PL/G micro-patterning nano fibrous membrane circular micro- Pattern structure and hydrophily is good.
By Fig. 2A2-C2Measurement result it is found that PL/G, Z-PL/G and DZ-PL/G micro-patterning nano fibrous membrane fiber Diameter is in 200nm or so.
By Fig. 2A3-C3It is found that the fibrous inside of PL/G micro-patterning nano fibrous membrane does not have a nano particle, Z-PL/G with The fibrous inside of DZ-PL/G micro-patterning nano fibrous membrane, which respectively corresponds, shows ZIF-67 and DMOG@ZIF-67 nano particle, Show that ZIF-67 and DMOG@ZIF-67 has been mixed in respective patterned fibrous film.
(3) the external drug of DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane and plasma diffusing W,Mo behavior
It is 2.0 × 2.0cm that DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane, which is cut into area,2Square Their weight is numbered and recorded to sample.In 37 DEG C, each sample is immersed in shaking table in 20mL PBS (pH=7.4), is shaken Bed hunting speed is 100r/min.Each time point collects the medium after 4mL release for detecting, and pours into isometric fresh PBS.Using UV-vis spectrophotometer, the DMOG content discharged in solution is collected in measurement at 230nm, as a result such as Fig. 3 A.Pass through The concentration of the Co ion discharged in inductively coupled plasma atomic emission spectrometry (ICP-AES) measurement composite membrane, as a result such as Fig. 3 B.
By Fig. 3 A it is found that the entire release process of DMOG is a positive slow release process, does not occur explosion type and release It puts.Release process continues to 25 days or so, and the medication amount of release has reached 70.7%.The speed of release is divided into two stages: One stage, the medication amount of release reached 49.2%, and rate of release is relatively slow to 11 days since release；It is later second In a stage, rate of release is more slow, and release amount of medicine reaches 70.7% at 25 days.
By Fig. 3 B it is found that with release time increase, Co ion concentration increase.To release 15 days, DMOG@ZIF-67/ The Co ion concentration of PLLA/Gel micro-patterning nano fibrous membrane release is 2.899 μM.
The micro-patterning nano fibrous membrane of 2 embodiment 1 of embodiment preparation is to cell in soft tissue injury injury of mouth repair process The influence of proliferation
PLLA/Gel micro-patterning nano fibrous membrane (PL/G), the micro- pattern of ZIF-67/PLLA/Gel prepared by embodiment 1 Change nano fibrous membrane (Z-PL/G) and DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) is cut respectively It at the round sheet of Φ=13mm, is sticked on cell climbing sheet, is impregnated 2 times in 75% alcohol, each 20min uses sterilizing PBS impregnates 2 times, each 10min, is finally putting into spare in 48 orifice plates.Respectively by HUVECs, HAFs, HaCaTs with every hole 7 × 103A cell density is inoculated in each group sample surfaces, and culture medium is added and is corresponding in turn to as 5%FBS and endothelial growth factor (ECGS) the DMEM culture medium of ECM culture medium, 10%FBS and 1640 culture mediums of 10%FBS, are put into 37 DEG C, 5%CO2's It is cultivated in cell incubator, replacement in culture medium every two days is primary.CCK8 development process detects the proliferation of three kinds of cells on the surface of the material Situation.Respectively at the 1st, 3 and 7 day of cell culture, CCK8 solution is added under the conditions of being protected from light in 48 orifice plates, in 37 DEG C of incubators It is incubated for 2~4h, Incubating Solution is added in 96 orifice plates, detects the light absorption value of developing solution at 450nm wavelength with spectrophotometer. CCK8 value indicates that absorbance is directly proportional to the quantity of material surface living cells with absorbance.
PLLA/Gel micro-patterning nano fibrous membrane (PL/G), ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (Z- ) and the vascular endothelial cell (HUVECs) of DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) PL/G Proliferative conditions such as Fig. 4 A.
PLLA/Gel micro-patterning nano fibrous membrane (PL/G), ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (Z- ) and the keratinocyte (HaCaTs) of DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) PL/G Proliferative conditions such as Fig. 4 B.
PLLA/Gel micro-patterning nano fibrous membrane (PL/G), ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (Z- PL/G) increase with the human fibroblasts (HAFs) of DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) Grow situation such as Fig. 4 C.
By Fig. 4 A-C it is found that vascular endothelial cell, keratinocyte and human fibroblasts are in the micro- pattern of PLLA/Gel Change nano fibrous membrane (PL/G), ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (Z-PL/G) and DMOG@ZIF-67/ Proliferative conditions on PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) are good, and cell number has the good time Dependence.Relative to PL/G group and Z-PL/G group, vascular endothelial cell, keratinocyte and human fibroblasts are in DZ-PL/ Proliferative capacity on G is most strong, and DZ-PL/G micro-patterning nano fibrous membrane has good cell compatibility.
Migration of the micro-patterning nano fibrous membrane to HUVECs and the influence at pipe ability of 3 embodiment 1 of embodiment preparation
PLLA/Gel micro-patterning nano fibrous membrane (PL/G), ZIF-67/ is added to 24 porocyte culture plates bottoms respectively PLLA/Gel micro-patterning nano fibrous membrane (Z-PL/G) and DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G), it is then placed in the cell transwell, the vascular endothelial cell that room is added that 600 μ L contain serum under cell soaks in advance The culture medium steeped, cell upper chamber access 100 μ L and contain 6 × 104A HUVECs is free of the culture medium of serum, in 37 DEG C, 5%CO2 It is incubated in incubator, the time is 6~8 hours, and violet staining observes cell migration situation.
PLLA/Gel micro-patterning nano fibrous membrane (PL/G), ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (Z- PL/G it) and under DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) effect, migrates to the cell of lower room Violet staining result is successively as shown in Fig. 5 A, B, C, and the analysis of HUVECs Quantitative cell migration is as shown in Figure 5 D, HUVECs cell Cell migration ability under DZ-PL/G effect is most strong, and it is best to promote cell migration effect.
Matrigel matrigel is placed in 4 DEG C of refrigerators on ice to thaw overnight, 96 orifice plates are placed in pre-cooling in -80 DEG C of refrigerators.To 50 μ Lmatrigel matrigels are added in pretreated 96 orifice plate, is put in 37 DEG C of incubators and is incubated for 30min, so as to Matrigel polymerize.After Matrigel polymerization, every hole, which is added, contains 1 × 104The each group material leaching liquor of a HUVECs is (empty White group (Ctrl), PL/G group, Z-PL/G group and DZ-PL/G), it is put in 37 DEG C of incubators after continuing culture 8 hours and observes cell At pipe situation.
PLLA/Gel micro-patterning nano fibrous membrane (PL/G), ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (Z- PL/G) and under DMOG@ZIF-67/PLLA/Gel micro-patterning nano fibrous membrane (DZ-PL/G) effect, HUVECs cell is at blood vessel For figure as shown in Fig. 6 A, B, C, HUVECs cell is as shown in Figure 6 D at blood vessel quantitative analysis, and HUVECs cell is under DZ-PL/G effect It is best at vascular effects.
The micro-patterning nano fibrous membrane of embodiment 4 embodiment 1 preparation is to HUVECs at blood vessel gene expression ability It influences
HUVECs cell is seeded in respectively on each group material (PL/G, Z-PL/G and DZ-PL/G), after culture to 48h, is moved Culture medium is removed, PBS is washed 2 times, and 1mL Trizol is added, sufficiently blows and beats, cell and tunica fibrosa is added to 1.5mL centrifuge tube together In.Cell RNA is extracted, RNA is obtained by reversion and obtains cDNA.The HUVECs cDNA that reverse transcription is obtained dilutes 5 times, experiment When draw 2 μ l as template, use SYBR Green (Takara, Japan) fluorescent dye.The angiogenesis of experimental verification is related Gene is VEGF, e-NOS, HIF1 α, and expression activity is as shown in Figure 7.
As shown in Figure 7, DZ-PL/G effect under, VEGF, e-NOS, HIF1 α gene expression activity be all remarkably higher than PL/G And Z-PL/G.Under Z-PL/G effect, the expression activity of VEGF, e-NOS gene is significantly higher than PL/G, and the expression of HIF1 α gene is living Property is suitable with PL/G.
Holostrome wound repair is tested in 5 body of embodiment
The male BALB/c experimental mouse of 30 18g is induced to suffer from diabetes using STZ, blood glucose, blood glucose value are surveyed in induction after a week It increases and numerical stability is in 250mg/dl, illustrating that mouse is successfully induced is diabetic mice, is used for subsequent experiment.
The skin wound (round, diameter 8mm) of a complete thickness is established in diabetic mice dorsal area, small Mouse wound area is implanted into the micro-patterning nano-fiber material of the preparation of embodiment 1 respectively and is grouped, and is respectively as follows: blank control Group (Control), PL/G group, Z-PL/G group, DZ-PL/G group.Utilized digital camera in fixed respectively at 0,3,7,9 and 11 day The wound healing situation of change of distance and angle recordings wound area, such as Fig. 8 A.According to Fig. 8 A, the diabetic mice back of production Wound repair simulates effect picture such as Fig. 8 B, diabetic mice back wound repair statistical chart such as Fig. 8 C of production.
By Fig. 8 A-C it is found that at the 7th day, DZ-PL/G group diabetic mice back wound area reduces by 74.6%, Z-PL/G Group reduces by 74.9%, PL/G group and reduces 73.9%, Control group reduction 62.6%；At the 11st day, DZ-PL/G group diabetes are small 95.3%, the Z-PL/G group that mouse back wound area reduces reduces 93.8%, PL/G group reduction 91.2%, the reduction of Control group 88.1%.Opposite Control group, PL/G group and Z-PL/G group, DZ-PL/G group diabetic mice speed of wound healing is obviously more Fastly, wound healing promoting significant effect.
The micro-patterning nano fibrous membrane of 6 embodiment 1 of embodiment preparation to the influence of wound repair quality in Mice Body and Its Related Mechanism
6.1 wound area histomorphometric analysis
The experiment mice that embodiment 5 is put to death when 7 days and 11 days, takes out the tissue specimen (2mm around wound area Left and right) carry out fabric analysis.
After the tissue specimen of acquirement is fixed 36h with 4% paraformaldehyde, using classification alcohol and dimethylbenzene to organize into Row dehydration, and utilize paraffin embedding.5 μ m-thicks are cut using RM2155 slicer to be sliced, and are used as using Masson trichrome stain and are seen Examine the formation of collagenous network and epidermis migration situation at wound tissue.Utilize Image Pro Plus version 6.0 (Media Cybernetics, Rockville, MD, USA) counts collagen forming amount, and wherein blue-green indicates collagenous fibres.
At 7 days and 11 days, each group mouse (Control group, PL/G group, Z-PL/G group and DZ-PL/G group) wound Masson ' s trichrome stain figure is as shown in Figure 11 A, B, and the black dotted lines box position of Image to left epidermis occurs and moves in Figure 11 A, B It moving, right side picture corresponds to the enlarged drawing of black dotted lines frame portion position in Image to left in Figure 11 A, B, and epidermis migration effect is better, The more blue dyeing the more significant.Relative to Control group, PL/G group and Z-PL/G group, DZ-PL/G group is more conducive to wound epidermis The regeneration of cell.
At 7 days and 11 days, each group mouse (Control group, PL/G group, Z-PL/G group and DZ-PL/G group) wound unit The collagen content of area is as shown in Figure 11 C, D, and at 11 days, DZ-PL/G group unit area collagen content is apparently higher than Control Group, PL/G group, Z-PL/G group.
Q-PCR assesses the expression of collagen deposition related gene in each group mouse wound tissue, as a result such as Figure 12, DZ-PL/G The collagen I of group, collagen I II, Ki67 expression are apparently higher than Control group, PL/G group and Z-PL/G group, the expression of TGF-β It is also DZ-PL/G group highest.
The analysis of 6.2 immunohistofluorescence stains
The skin that 5 experiment mice wound location of embodiment was obtained respectively at the 7th day and 11 days, using Stereo microscope to wound The case where oral area position is taken pictures, and wound angiogenesis is observed.(5 μm) of tissue specimen after slice are passed through into dewaxing treatment, Impregnate 20min in 100 DEG C of sodium citrate buffer, be cooled to room temperature 1h, after at 4 DEG C carry out primary antibody (CD31) hatching Overnight.Then, it is immersed in PBS and is cleaned, carry out 2h hours secondary antibody hatching processes at room temperature.Finally, with DAPI to thin Karyon is dyed.Observation analysis is carried out using fluorescence microscope (Leica Confocal microscope).
At the 7th day and the 11st day, each group diabetic mice (Control group, PL/G group, Z-PL/G group and DZ-PL/G group) The angiogenesis situation of wound area tissue such as Fig. 9 A, can be observed the new vessels of DZ-PL/G group obviously compared with more than other groups, The blood vessel of wound more crypto set.
At the 7th day and the 11st day, the new vessels statistical result of each group diabetic mice unit area such as Fig. 9 B, C, DZ- PL/G has the effect of significantly promoting angiogenesis.
At the 7th day and the 11st day, the histogenic immunity of each group diabetic mice angiogenesis marker CD31, DAPI, Merge Fluorogram such as Figure 10 A, B, compared to Control group, the expression of PL/G group, Z-PL/G group, DZ-PL/G group CD31 is obviously increased, Illustrate that its angiogenine content obviously increases.
At the 7th day and the 11st day, each group diabetic mice CD31 marks new vessels statistical result such as Figure 10 C, D, DZ- PL/G has apparent promotion angiogenesis effect.
To sum up, DZ-PL/G group can remarkably promote the expression of CD31, can dramatically increase the new life of wound area blood vessel.
The gene expression analysis of 6.3 proinflammatory cytokines
Cross the total serum IgE that Trizol extracts again the skin histology of epithelialization.CDNA is synthesized, Prime is used Isolated RNA (1 μ g) is inverted 30 minutes at 37 DEG C respectively and is inverted 10 at 85 DEG C by ScriptTM RT Master Mix Second.Q-PCR test is carried out using SYBR Green detection reagent, uses actin as reference gene.
It is proinflammatory thin in each group (Control group, PL/G group, Z-PL/G group and DZ-PL/G group) diabetic mice wound tissue The expression of intracellular cytokine IL-10, IL-6 and IL-1 β, as shown in figure 13.The result shows that DZ-PL/G group can significantly lower IL-10, The expression (Figure 13 A-C) of IL-6 and IL-1 β.

Claims (10)

1. a kind of be compounded with the micro-patterning nano-fiber material for carrying medicine MOF, which is characterized in that hydrophilic with what is be intertwined Property composite electrostatic spinning nanofiber be skeleton, ordered arrangement micro-patterning structure, and be distributed the porous of open three-dimensional perforation Structure；Hydrophily composite electrostatic spinning nanofiber is supportive biocompatible material, hydrophily biocompatible material and load The blend of the metal organic frame nano particle of repairing activity molecule.
2. micro-patterning nano-fiber material according to claim 1, which is characterized in that the supportive bio-compatible material Material includes l-lactic acid, polycaprolactone, chitosan or chitin, and hydrophily biocompatible material includes gelatin or hyalomitome The partial size of acid, metal organic frame nano particle is 50~500nm, and repairing activity molecule includes repairing activity drug and/or day The right repairing activity factor.
3. micro-patterning nano-fiber material according to claim 1, which is characterized in that hydrophily composite electrostatic spinning is received In rice fiber, the metal of supportive bioactive materials, hydrophihc bioactive material and load repairing activity molecule has machine frame The mass ratio of frame nano particle is 1:0.5~2:0.5 × 10-3~5 × 10-3。
4. being compounded with the preparation method for carrying the micro-patterning nano-fiber material of medicine MOF described in claims 1 to 3, feature exists In step includes: the reception template using micro-patterning, with the evenly dispersed metal organic frame for having load repairing activity molecule The organic solvent of nano particle, supportive bioactive materials and hydrophihc bioactive material makees spinning solution, electrostatic spinning system It is standby to be compounded with the micro-patterning nano fibrous membrane for carrying medicine MOF.
5. the preparation method according to claim 4, which is characterized in that supportive bioactive materials, hydrophilic in spinning solution Property bioactive materials and load repairing activity molecule metal organic frame nano particle mass ratio be 1:0.5~2:0.5 ×10-3~5 × 10-3, supportive bioactive materials and the gross mass of hydrophihc bioactive material and the volume of organic solvent Ratio be 1g:5~20mL；
The supportive biocompatible material includes l-lactic acid, polycaprolactone, chitosan or chitin；
Hydrophily biocompatible material includes gelatin or hyaluronic acid；
Repairing activity molecule includes repairing activity drug and/or the natural repairing activity factor；
Organic solvent includes hexafluoroisopropanol, methylene chloride, chloroform or trifluoroethanol.
6. the preparation method according to claim 4, which is characterized in that the parameter of electrostatic spinning are as follows: room temperature, 40%RH~ 60%RH, application voltage be 7~9kV, solution fltting speed be 0.01~0.03mL/min, spray head and patterning receive template it Between distance be 8~12cm.
7. the preparation method according to claim 4, which is characterized in that the metal organic frame of load repairing activity molecule is received The preparation step of rice grain includes: that metal organic frame nano particle is dipped in the solution containing repairing activity molecule, repairs and lives Property molecule be carried in the duct of metal organic frame nano particle, formed load repairing activity molecule metal organic frame receive Rice grain.
8. preparation method according to claim 7, which is characterized in that the preparation step packet of metal organic frame nano particle It includes: metal salt and organic ligand molecule is dissolved in organic solvent, reaction prepares metal organic frame under constant temperature and stirring condition Nano particle.
9. application of any one of the claim 1-3 micro-patterning nano-fiber material in terms of preparing wound repair material.
10. a kind of biomaterial has wound repair activity, which is characterized in that contain any one of claim 1-3 micro- figure Patterned nanometer fibrous material.
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Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110433333A (en) * 2019-08-16 2019-11-12 上海师范大学 A kind of metal organic frame/electrospinning fibre composite material and preparation method and application with NO and copper ion sustained release synergistic effect
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101829361A (en) * 2009-03-10 2010-09-15 广州迈普再生医学科技有限公司 Nano-bionic material for tissue repair and preparation method thereof
WO2013007224A1 (en) * 2011-07-14 2013-01-17 Primecell A.S. Cell culture substrate and a method for producing thereof
CN103006359A (en) * 2012-12-24 2013-04-03 汪泱 Bionic three-dimensional tissue engineering scaffold and preparation method thereof
CN107551311A (en) * 2017-08-25 2018-01-09 上海师范大学 A kind of porous composite electrospun tunica fibrosa of orientation of controlled drug release and its preparation method and application
CN107715174A (en) * 2017-09-30 2018-02-23 清华大学 A kind of bionical tissue engineering bracket containing micropore and nanofiber composite construction and preparation method thereof
CN109381732A (en) * 2017-08-03 2019-02-26 国家纳米科学中心 Electrostatic spinning dressing, preparation method and the application of growth factor-loaded micromolecular inhibitor

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101829361A (en) * 2009-03-10 2010-09-15 广州迈普再生医学科技有限公司 Nano-bionic material for tissue repair and preparation method thereof
WO2013007224A1 (en) * 2011-07-14 2013-01-17 Primecell A.S. Cell culture substrate and a method for producing thereof
CN103006359A (en) * 2012-12-24 2013-04-03 汪泱 Bionic three-dimensional tissue engineering scaffold and preparation method thereof
CN109381732A (en) * 2017-08-03 2019-02-26 国家纳米科学中心 Electrostatic spinning dressing, preparation method and the application of growth factor-loaded micromolecular inhibitor
CN107551311A (en) * 2017-08-25 2018-01-09 上海师范大学 A kind of porous composite electrospun tunica fibrosa of orientation of controlled drug release and its preparation method and application
CN107715174A (en) * 2017-09-30 2018-02-23 清华大学 A kind of bionical tissue engineering bracket containing micropore and nanofiber composite construction and preparation method thereof

Cited By (23)

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